Evidence from neuroimaging studies indicate that individuals with bipolar
disorder exhibit altered functioning of the brain’s fronto-limbic systems
implicated in voluntary emotion regulation. Few studies, however, have examined
the extent to which unaffected youth at familial risk for bipolar disorder
exhibit such alterations.

Using an fMRI emotional working memory paradigm, Dr. Ladouceur, Phillips,
Birmaher, and colleagues in the Department of Psychiatry at the University of
Pittsburgh investigated the functioning of fronto-limbic systems in fifteen
healthy bipolar offspring (8–17 years old) with at least one parent diagnosed
with bipolar disorder, and 16 age-matched healthy control participants. Neural
activity and functional connectivity analyses focused on a priori neural regions
supporting emotion processing (amygdala and ventral striatum) and voluntary
emotion regulation (ventrolateral prefrontal cortex (VLPFC), dorsolateral
prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC)).

Relative to healthy controls, bipolar offspring with at least one parent
diagnosed with bipolar disorder exhibited greater right VLPFC (BA47) activation
in response to positive emotional distracters and reduced VLPFC modulation of
the amygdala to both the positive and negative emotional distracters; there were
no group differences in connectivity for the neutral distracters. Findings from
this study demonstrate, for the first time, that alterations in the functioning
of fronto-limbic systems implicated in voluntary emotion regulation are present
in unaffected bipolar offspring. Future longitudinal studies are needed to
determine the extent to which such alterations represent neurodevelopmental
markers of risk for future onset of bipolar disorder.